The harmful effects of radiation, chemotherapeutic drugs, and other chemicals on spermatogenic cells will be examined. The effects to be considered are killing of stem cells which could result in sterility and alterations in the DNA which could produce genetic mutations. Quantitative measurements of mouse testicular stem cell survival will be performed by histological methods and sperm counts. Additional chemicals, dose regimes, and combinations of chemicals will be tested by these methods. The hypothesis that measurements of stem cell survival are sufficient to predict the eventual return to fertility will be tested by measuring these parameters with several different cytotoxic treatments. Mutagenic alterations in DNA produced by radiation or drugs in mouse testicular cells will be assayed. Alterations in DNA content of individual mouse spermatids or sperm will be determined by flow cytometry. Heritable genetic damage after adriamycin treatment will be studied by analyzing, in the post-sterile peiod, for dominant lethal mutations, and semi-sterility, translocations and sperm abnormalities in the offspring. Sperm in human semen ejaculates from cancer patients who have received chemotherapy will be analyzed. Sperm counts will be performed prior to and at selected intervals following chemotherapy in order to determine whether the treatment has a sterilizing effect and the time course of the return to fertility. In a collaborative study, morphological sperm abnormalities will be scored in order to determine whether this parameter could detect genetic mutations resulting from chemotherapy regimes. Possible mutations will also be analyzed by flow cytometry.